Innovation - the key to medical breakthroughs

Innovation the key to medical
breakthroughs
Renowned early 19th century French chemist and
microbiologist Louis Pasteur once said “chance
favours the prepared mind”. While serendipity
plays an important role in scientific breakthroughs,
it is the ability to recognise the potential of a chance
discovery and turn it into something useful and
innovative that exemplifies a truly great scientist.
Scientists at the Malaghan Institute of Medical
Research strive to be at the forefront of innovation
and creativity, and in this issue of Scope we
showcase our asthma research programme as
an example of this. We also discuss how our
scientists are using techniques learned through
researching cancer to study a rare disease that has
no known cure, and how they are applying their
knowledge of therapy-resistant cancer cells to the
development of treatments for neurodegenerative
diseases.
In doing so, our scientists are challenging the
way we currently treat certain diseases and offer
practical solutions for how we might improve these
therapies in the future.
“The Malaghan Institute and its supporters
seek to ensure that the combination of
‘chance and prepared minds’ is backed up
by a world class laboratory infrastructure
and a commitment to translating
discoveries into meaningful outcomes.”
Prof Graham Le Gros, Director.
Malaghan Institute Immunologist Prof Franca Ronchese,
whose cancer research has opened the door to a
potential immunotherapy for asthma.
While establishing his asthma research
programme at the Malaghan Institute in the
mid-1990s, Prof Graham Le Gros observed that
certain types of bacterial lung infection could
actually halt the development of asthma in
mice. This pivotal discovery made the front
cover of the prestigious New Scientist magazine
and has led to a new form of therapy that could
revolutionise the way we treat asthma.
For parents of children who suffer repeated severe
asthma attacks, life is a daily battle. Asthma is the
consequence of an overactive immune system,
causing inflammation in the lungs. The steroid
inhalers that are used to treat the disease work by
reducing the inflammation in the lung so it is easier
to breathe. However, there is growing concern
regarding their long-term use.
It has been proposed that the recent increased
prevalence and severity of asthma, particularly
among children, is a consequence of the Western
world’s obsession with cleanliness. The so-called
‘Hygiene Hypothesis’ suggests that some people
react to harmless environmental stimulants such
as pollen or house dust mites because as infants
they were not exposed to the infections required
to fully develop their immune systems.
Prof Le Gros’ research group decided to test this
hypothesis by looking to see if they could restore
‘immune balance’ in experimental asthma models
with controlled bacterial infections. Strikingly their
research showed that treatment with the bacteria
used to make the TB vaccine, actually prevented
the inflammatory immune responses normally
associated with asthmatic lungs. This research
revealed a new way of potentially treating asthma
- by simply giving the immune system something
else to focus on!
Three year old Dylan Carson who is affected by asthma. His
mum Jacqui, who works at the Malaghan Institute, welcomes
the news that an asthma vaccine is being developed, providing
another treatment option for parents of asthmatic children.
Prof Le Gros’ published scientific paper describing
this landmark discovery has been extensively
cited and used by scientists, clinicians and drug
companies to identify safer versions of the bacteria
and their extracts for the development of a vaccine
to treat asthma in humans. There are now several
new compounds being developed in the USA that
are in the late stages of clinical trial and the FDA
approval process – a wonderful testament to the
original pioneering research undertaken by Prof
Le Gros’ research group here at the Malaghan
Institute.
Prof Franca Ronchese and colleagues at the
Malaghan Institute have spent over 15 years
developing a cancer vaccine that works by
stimulating the immune system to attack a
patient’s tumour. One of the biggest hurdles
they have faced is maintaining the intensity of
the immune response over time.
Part of the reason for this is that under certain
conditions specialised cells called cytotoxic T
lymphocytes (CTLs) attack and kill the dendritic
cells before they can do their job. Although
dendritic cell killing is a stumbling block for a
cancer vaccine, Prof Ronchese made the pivotal
connection that this same phenomenon could
be used to tone down the immune response in
diseases where the immune system is overactive,
such as asthma. Her research group went on to
make the striking discovery that stimulating CTLs
to get rid of dendritic cells in the airway prevented
the development of allergic airway inflammation in
an experimental model of acute disease.
This exciting research received HRC funding earlier
this year to further explore the potential of CTL
immunotherapy as a treatment for allergic asthma.
This is a fine example of how a problem presented
in one area of research has the potential to provide
a breakthrough in another. The key to undertaking
science that redefines our understanding and
treatment of disease is in recognising such
opportunities when they appear.
From left, immune cell biology researchers Evelyn Hyde,
Joel Ma, Dr Mark Yang and Prof Franca Ronchese.
• Asthma is a chronic respiratory disease of major concern in NZ
• It affects 1 in 4 children and 1 in 6 adults
•D
uring an asthma attack the lining of the bronchial tubes swells, causing the airways to narrow
- this makes it hard to breathe in and even harder to breathe out
•T
he final symptoms of allergic asthma are due to activation of the Th2 immune response
(which normally serves to protect us from parasite infections) by harmless environmental
triggers such as pollen or house dust mites
•T
he current treatment for asthma is the use of steroid based preventer inhalers, which work
to decrease airway inflammation
Issue 43, 2010
Senior Malaghan Institute scientist Dr Melanie
McConnell has built an entire research
programme around finding ways to identify and
kill cancer stem cells – a rare population of cells
found within tumours that are thought to be the
main cause of relapse and metastasis. Ironically,
this research has led to an innovative spin-off
programme focused on keeping cells alive.
Cancer stem cells have the unique ability to renew
themselves and use an extensive network of
survival mechanisms to evade chemotherapy and
radiotherapy treatments. As her understanding
of these survival pathways grew, Dr McConnell
LAM
or
Lymphangioleiomyomatosis
is
a devastating progressive lung disease
that few have heard of. However, for the
21 New Zealand women who suffer from the
disease, LAM is a big deal.
LAM causes shortness of breath, chest pains,
coughing and lung collapse and there is no known
cure. Because LAM is so rare it doesn’t receive a
lot of attention. Malaghan Institute scientists Prof
Mike Berridge and Dr James Baty hope to change
this by using their innovative cancer research to
help LAM sufferers in a small but significant way.
Although LAM is not presently classified as a
cancer, LAM cells have cancer-like properties
such as loss of cell growth control, mutations
and the ability to spread elsewhere in the body.
With support from the NZ LAM Trust and the LAM
Australasia Research Alliance, Dr Baty is taking a
closer look at LAM cells to find out if there is a
small population of cells with cancer stem cell-like
properties. If these cells exist in LAM, they will
need to be targeted for effective LAM therapy.
realised that cancer stem cells might just hold
the secret to extending the life of cells that die
prematurely, as in motor neurone disease.
Patients with motor neurone disease suffer
increasing weakness of the muscles, due to the
death of the neurons that feed into them and there
is currently very little that can be done to stop this.
Dr McConnell, with support from the estates of
Ellen, Sinclair, Barbara and Alison Wallace, hopes
to develop approaches that actually prolong the
survival of neurons – a creative flip-side to her
usual role of trying to kill cancer stem cells.
Dr Baty says the driving force behind his research
is his desire to help people for whom there are
very few treatment options currently available.
He enjoys the challenge of deciphering the many
signalling pathways involved with cell growth,
proliferation and survival that are deregulated in
LAM patients, and believes the most effective
approach for treating these individuals might
be with immunological therapies and/or drug
treatments currently in use for cancer patients.
Both Dr Baty and LAM Trust Director Bronwyn
Gray recently attended the 1st European LAM
Conference held in Udine, Italy.
Dr James Baty
pictured with NZ
LAM Trust Director
Bronwyn Gray, who
has spent the past
11 years raising
awareness and
funds for research
into LAM. For further
information on
the NZ LAM Trust,
please visit
www.lam.org.nz.
A timeline of the Malaghan Institute’s major achievements in medical research
Causes of atherosclerosis
– significant new knowledge
generated in understanding basis
for atherosclerotic plaque formation
during cardiovascular disease
Breakthrough in understanding
blood cell formation – discovered
that erythropoietin promotes
platelet production
1980-1995
Using TB vaccine to block
development of allergic
asthma – discovered that
specific kinds of bacterial
lung infections alleviated the
symptoms of allergic asthma
in experimental models
Adjuvant for improved
cancer vaccine –
discovered compound
extracted from marine
bacteria can greatly
improve anti-tumour
immune responses
2000
Early gout detection
– gouty arthritis clinical
study identified markers
of disease susceptibility
Potential
immunotherapy for
asthma – discovered
that killing of airway
dendritic cells
improves allergic
airway inflammation
2006
1997
Green chemistry – less
toxic chemical process
developed for making
a specific class of
chemical compounds
used in medical therapy
First in NZ to receive
Medsafe approval
of GMP laboratory
for the manufacture
of cellular vaccines
against cancer
2005
TB vaccine
development –
identified BCG vaccine
induced immune cells
that provide long-term
protection against TB
2008
2007
2009
2010
2003
Vaccine for treating
cancer – discovered
novel method for
making a vaccine
against tumours that
uses the body’s own
dendritic cells and
tumour tissue
Novel therapy for
multiple sclerosis –
discovered that a toxin
from bacteria could be
used to treat disease
symptoms of MS in a
laboratory model of the
disease
Development of high
throughput drug discovery
assay – based on novel enzymatic
pathway used by cancer cells
and inflammatory cells to meet
their energy and metabolic
requirements
This newsletter was generously supported by:
Identification of arthritis
drug candidates from NZ
environment – used drug
discovery assay to screen
NZ’s marine and terrestrial
plants and organisms,
identified lead compounds
with anti-inflammatory activity
Hookworm vaccine –
made pivotal discovery
that could lead to a vaccine
against hookworm, a parasite
that plagues an estimated
one billion people worldwide
Our scientists in the spotlight
Launch into Inner Space
“Ever Wondered?”, a new science show on TVNZ 7, takes
you behind the scenes to look at what is being achieved at
the cutting edge of science in NZ. Kylie Price, the Institute’s
Flow Cytometry Manager, along with Neurosurgeon
and Malaghan Clinical Research Fellow Mr Martin Hunn,
recently featured in an episode that looked at how science
and technology is aiding medical research. Another
Malaghan Institute scientist who you may have caught a
glimpse of on TV recently is Infectious Diseases Group
Leader, Dr Joanna Kirman. Dr Kirman was filmed for the
TV3 show ‘What’s really in our...’ discussing bacteria and
viruses in the episode on ‘Soaps and Cleansers’.
Long time supporter and leading NZ Fashion Designer,
Petrena Miller, has created some unique fashion
garments for a new range called “Inner Space”. These
tops are available for sale through retailers in NZ and
Australia with a percentage of sales donated to the
Malaghan Institute. First revealed on the catwalk during
the Auckland Friends’ fundraiser, these garments
display an image of a dendritic cell that has been turned
into something very funky and fashionable. They make
great gifts for yourself or for others (there is even a
T-Shirt for the guys!). Visit www.malaghan.org.nz/
inner_space/ to find your nearest retailer.
‘Inner Space’
garments
from Petrena
Miller Designs
– modelled
at Malaghan
fashion
fundraiser.
Flow Cytometry Suite Manager, Kylie Price, being filmed
for an episode of TVNZ 7’s Ever Wondered?
Science Learning Hub website
Our scientists have also been sharing their knowledge
and passion for science on the Science Learning Hub
website. Managed by the University of Waikato, this
website provides resources for teachers of school
years 5-10 and is developed in collaboration with NZ
scientists. Keep an eye out for our scientists in the
upcoming section entitled ‘Fighting Infection’ on
www.sciencelearn.org.nz.
AMI Insurance – supporting valuable research
AMI Insurance has again shown its wonderful support
for the Malaghan Institute by confirming their principal
sponsorship of the upcoming Auckland charity golf
tournament. AMI’s partnership with the Institute has
spanned more than a decade and their generosity has
included the sponsorship of our annual Lollipop Appeal,
Asthma Laboratory and many Friends fundraising
events. A huge thank you to John Balmforth (CEO) and
his team at AMI Insurance and our congratulations on
their recent ‘Services to the Community’ award from
the 2010 Australia and New Zealand Insurance and
Finance Industry Awards.
Recent grants
We are thrilled with the response we have received
between July and September 2010. Thanks to these
organisations for their great support:
Infinity Foundation Ltd
Clyde Graham Charitable Trust
HB Williams Turanga Trust
The Southern Trust
Up-coming events
STOP PRESS! The Malaghan Institute will be
involved with Wellington’s Inaugural Cancer
Symposium in February 2011, which will feature top
cancer clinicians from the world-renowned Mayo
Clinic in Rochester, Minnesota, USA. To find out
more, visit www.malaghan.org.nz.
2010 MALAGHAN CHARITY GOLF TOURNAMENT
REMINDER... Hawkes Bay (Friday 29th October),
Wellington & Auckland (Friday 12th November).
For further details, please contact Vicky Hale on
04 499 6914 x821 or vhale@malaghan.org.nz.
PO Box 7060, Wellington 6242, NEW ZEALAND
Ph +64 4 499 6914 Email mimr@malaghan.org.nz
www.malaghan.org.nz